The DNA damage response is a description of how a cell responds when challenged with agents that modify DNA or perturb DNA metabolism. For example, ultraviolet (UV) radiation damages specific bases within the DNA duplex. This damage creates problems for DNA and RNA polymerases as they try to read the DNA code to either produce a copy of the DNA or to make RNA. Fortunately, cells have mechanisms that can sense and repair the DNA lesion. The cell coordinates this repair with its efforts to replicate and divide. It is far better for the cell to repair the damage prior to attempting DNA replication since replication can convert the damage into a mutation. This coordination of cell cycle activities with DNA repair is called a checkpoint. Essentially, the cells check that everything is OK prior to proceeding in their effort to duplicate. Finally, if the amount of DNA damage overwhelms the repair capacity of the cell then it will initiate programmed cell death. The death of the cell is preferable to the possibility that the cell will survive with an altered genome in a multicellular organism since the alterations in the genome can cause cancer.
Biochemically, the DNA damage response is really a signal transduction pathway that contains sensors of the DNA damage, mechanisms to disseminate a signal that a problem exists, and executing proteins that change their function to deal with the problem. Sensor proteins must be able to discriminate between normal and damaged DNA. The dissemination mechanisms rely mostly on changes in protein phosphorylation, and the downstream targets of this signaling pathway include master regulators of the cell cycle, DNA repair proteins, transcription factors, the replication machinery, and many other protein activities that help a cell to cope with the DNA damage.